Preparation and Neuroprotective Effects of Bergamot Essential Oil Liposomes in a PC12 Cell Model of Alzheimer’s Disease

Bergamot essential oil (BEO) exhibits anxiolytic and antidepressant properties but its biomedical use is restricted by poor solubility, volatility, and instability. Liposomal encapsulation offers a strategy to enhance the stability and bioavailability of volatile plant-derived compounds. In this study, BEO-loaded liposomes were prepared with varying cholesterol-to-lecithin ratios and evaluated for their physicochemical properties and neuroprotective effects in a PC12 cell model of Alzheimer’s disease (AD) induced by amyloid-β fragment Aβ25–35. Liposomes formulated at cholesterol-to-lecithin ratios of 1:4 and 1:5 demonstrated optimal characteristics, with mean particle sizes below 170 nm, narrow size distribution (PDI < 0.2), high surface charge (zeta potential > 30 mV), and encapsulation efficiencies of 70–90%. Cytotoxicity assays confirmed that 20 µM Aβ25–35 reduced PC12 cell viability by 56.41%, increased apoptosis, and induced G0/G1 cell cycle arrest. Pretreatment with BEO liposomes (0.03 mg/mL) significantly improved cell viability, alleviated apoptosis, and mitigated cycle arrest. These findings suggest that liposomal delivery enhances the stability and bioactivity of BEO, enabling protection against Aβ-induced neurotoxicity. The study provides experimental evidence supporting BEO liposomes as a promising neuroprotective formulation for AD intervention.